The scavenger receptor BI is a cell surface lipoprotein receptor for selective high-density lipoprotein (HDL) cholesterol uptake in the liver and steroidogenic tissues. Studies of genetically manipulated strains of mice have revealed that SR-BI plays a key role in regulating HDL metabolism, cholesterol transport to steroidogenic tissues and bile cholesterol secretion. Furthermore, SR-BI protects against the development of atherosclerosis and is required for normal female fertility. If SR-BI has similar functions in lipoprotein metabolism and atherosclerosis in humans, it may represent a new target for the prevention and/or treatment of atherosclerotic cardiovascular disease.